Neurobiological and Clinical Markers for a Severe Form of Alcoholism in Women.

It is now well established that a person's risk for developing alcoholism(1) tends to reoccur in families (Hill et al. 1977; Cotton 1979; Hill et al. 1987; Hill 1994). Although alcoholism is clearly familial, the role of genetics in a person's vulnerability to develop alcoholism continues to be debated. Most researchers would support the notion that some genetic influence occurs. The question to be asked is: How much of the variation between people in susceptibility to alcoholism is explained by genetic factors? It is also important to ask: How is genetic vulnerability moderated by personal factors (e.g., gender, age, and co-occurring psychiatric disorders) and environmental ones (e.g., cultural milieu and shared familial environment)? This review will discuss the role of genetic factors in the development of alcoholism in women. The data were obtained from the author's large, high-density-for-alcoholism pedigree study(2) of women. The article will discuss (1) the most recent studies of event-related potential(3) differences in women and their offspring and (2) the clinical characteristics of their offspring. EVIDENCE FOR GENETIC MEDIATION IN WOMEN Several types of studies traditionally have been used in attempts to clarify the contribution of genetic influences to alcoholism, including family, adoption, and twin studies. Some of these studies support a genetic role in women's alcoholism. Family Data The first study to investigate the familial transmission of alcoholism separately for men and women alcoholics was completed by Cloninger and colleagues (1978). Applying a model (of transmission) that included both genetic and environmental factors, Cloninger and colleagues (1978) concluded that the difference in alcoholism prevalence observed between men and women resulted entirely from cultural or nonfamilial environmental factors. Based on the most recent epidemiological data, the ratio of male to female alcoholism is 2:1 in the general population (Kessler et al. 1994). Cloninger and colleagues found that equal numbers of alcoholic relatives were counted among both male and female alcoholics in their early study, suggesting that both genders have an equal likelihood that their disorder is inherited or is genetically mediated. Adoption Studies In further support of alcoholism's familial nature, one line of research has indicated that the disease is more likely to be transmitted within families than are most psychiatric disorders (Merikangas et al. 1985). This high transmissibility could, however, result from the family environment (e.g., exposure to an alcoholic parent) rather than from genetic factors. In seeking to separate these two possible influences, a now-classic study of adopted children that concerned the etiology of alcoholism in men (Goodwin et al. 1973) suggested that transmission can occur even in the absence of exposure to an alcoholic parent. Few adoption studies have been conducted that address genetic factors in women's alcoholism. Thus, the conclusions that can be reached about genetic transmission based on adoption studies in women are tentative (Hill and Smith 1991; Hill 1993). Three adoption studies have been conducted that report results for female adoptees, one each in Sweden (Bohman et al. 1981), Denmark (Goodwin et al. 1977), and the United States (Cadoret et al. 1985). The Swedish and Danish studies found too few alcoholic women to warrant any conclusions. However, Cadoret and colleagues (1985) had a sufficiently large sample to conclude that genetic factors operated in the etiology of female alcoholism (for further discussion of adoption research, see the article by Cadoret, pp. 195-200). Twin Studies Further evidence for the genetic mediation of alcoholism in women can be gained from studies that have examined whether members of adult twin pairs match their twins in alcohol-related behaviors. This research compares the agreement in behavior between members of identical twin pairs (i. …

I t is now well established that a per son's risk for developing alcoholism 1 tends to reoccur in families (Hill et al. 1977;Cotton 1979;Hill et al. 1987;Hill 1994). Although alcoholism is clearly familial, the role of genetics in a person's vulnerability to develop alcoholism con tinues to be debated. Most researchers would support the notion that some genet ic influence occurs. The question to be asked is: How much of the variation be tween people in susceptibility to alco holism is explained by genetic factors? It is also important to ask: How is genetic vulnerability moderated by personal fac tors (e.g., gender, age, and cooccurring psychiatric disorders) and environmental ones (e.g., cultural milieu and shared familial environment)? This review will discuss the role of genetic factors in the development of alcoholism in women. The data were obtained from the author's large, highdensityforalcoholism pedi gree study 2 of women. The article will discuss (1) the most recent studies of eventrelated potential 3 differences in women and their offspring and (2) the clinical characteristics of their offspring.

EVIDENCE FOR GENETIC MEDIATION IN WOMEN
Several types of studies traditionally have been used in attempts to clarify the contri bution of genetic influences to alcoholism, including family, adoption, and twin stud ies. Some of these studies support a genetic role in women's alcoholism.

Family Data
The first study to investigate the familial transmission of alcoholism separately for men and women alcoholics was completed by Cloninger and colleagues (1978). Applying a model (of transmission) that included both genetic and environmental factors, Cloninger and colleagues (1978) concluded that the difference in alco holism prevalence observed between men and women resulted entirely from cultural or nonfamilial environmental factors. Based on the most recent epidemiological data, the ratio of male to female alco holism is 2:1 in the general population (Kessler et al. 1994). Cloninger and col leagues found that equal numbers of alco holic relatives were counted among both male and female alcoholics in their early study, suggesting that both genders have an equal likelihood that their disorder is inherited or is genetically mediated.

Adoption Studies
In further support of alcoholism's familial nature, one line of research has indicated that the disease is more likely to be trans mitted within families than are most psy chiatric disorders (Merikangas et al. 1985). This high transmissibility could, however, result from the family environ ment (e.g., exposure to an alcoholic par 2 The term "high density for alcoholism" refers to families in which the chance of a relative of the alco holic's being alcoholic is far greater than it is in the general popultion (in Hill and colleagues' families, their risk is five times higher than in the general population). 3 The eventrelated potential is a specific measure of the brain's electrophysiological response to a perceived stimulus. ent) rather than from genetic factors. In seeking to separate these two possible influences, a nowclassic study of adopted children that concerned the etiology of alcoholism in men (Goodwin et al. 1973) suggested that transmission can occur even in the absence of exposure to an alcoholic parent. Few adoption studies have been conducted that address genetic factors in women's alcoholism. Thus, the conclusions that can be reached about genetic transmission based on adoption studies in women are tentative (Hill and Smith 1991;Hill 1993).
Three adoption studies have been conducted that report results for female adoptees, one each in Sweden , Denmark (Goodwin et al. 1977), and the United States (Cadoret et al. 1985). The Swedish and Danish studies found too few alcoholic women to warrant any con clusions. However, Cadoret and colleagues (1985) had a sufficiently large sample to conclude that genetic factors operated in the etiology of female alcoholism (for further discussion of adoption research, see the article by Cadoret,.

Twin Studies
Further evidence for the genetic mediation of alcoholism in women can be gained from studies that have examined whether members of adult twin pairs match their twins in alcoholrelated behaviors. This research compares the agreement in be havior between members of identical twin pairs (i.e., monozygotic [MZ] twins, whose genes are identical), with that of fraternal twin pairs (i.e., dizygotic [DZ] twins, who share an average of 50 percent of their genes). If a study finds twice the rate of agreement in the MZ twins as in the DZ twins, genetic influences are sug gested to be at work (for further discus sion, see the article by Prescott and SHIRLEY Y. HILL, PH.D., is a professor of psychiatry and director of alcoholism and genetics research in the Depart ment of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Kendler,. Agreement be tween members of twin pairs for both drinking behaviors (Heath et al. 1989) and alcohol dependence (Gurling et al. 1981;Pickens and Svikis 1988;Pickens et al. 1991;Kendler et al. 1992;McGue et al. 1992) have been studied.

RESEARCH UPDATE
Although three studies utilizing clinical samples (Gurling et al. 1981;Pickens and Svikis 1988;McGue et al. 1992) did not find that MZ twins differed from DZ twins in a pattern suggestive of a genetic role, recent reports by Pickens and colleagues (1991) and Kendler and colleagues (1992) are more convincing. For example, Kendler and col leagues, studying a sample of more than 1,000 female MZ and DZ twin pairs from the general population, found substantially higher correlations of alcohol dependence between female MZ twins than between DZ twins; they ascribed more than 50 percent of the variation in the degree of alcoholism risk (i.e., variance) seen in their sample to genetic factors (Kendler et al. 1995).

EVIDENCE FOR TWO TYPES OF ALCOHOLISM IN WOMEN
Twin and adoption studies support a genetic component in women's alcoholism. It is likely, however, that genetic factors make a greater contribution to some women's development of the disorder than to other women's. Genetic risk for developing alcoholism appears to exist on a continuum ranging from virtually no risk to exception ally high risk; the latter designation results from having a concentration of alcoholics in one's family (i.e., familial density). For simplicity of argument, however, the liability to develop alcoholism can be thought of as having two basic forms, distinguished by the extent to which each is influenced by genetic factors. Cloninger and colleagues (1981) de scribed two forms of alcoholism among men. Male type I alcoholics are those whose likelihood of drinking depends much more heavily on the environmental conditions under which they reside than on genetic influence. The type II male alcoholic, however, has been described as having familial alcoholism and as devel oping alcoholism at a much earlier age (i.e., early onset, often during adoles cence) and to a more severe degree than the type I male.
Accordingly, it is possible that two types of alcoholism exist in women. For example, studies by Glenn and Nixon (1991) and Lex and colleagues (1991) provide evidence for more severe symp toms in women with early onset alco holism (i.e., beginning before age 25). Women with the severe form of alco holism also come from families with a greater density of alcoholism among their members. Likewise, preliminary results from Hill and colleagues suggest a very early onset of alcoholism for female alco holics whose families display multigenera tional alcoholism (discussed below). This profile suggests that a form similar to type II male alcoholism may exist in women.
Some researchers, however, believe that all alcoholism in women is less severe than it is in men. For example, Gilligan and colleagues (1987) have used the term "femalelike" to describe a less severe and less genetically mediated form of alco holism in men (i.e., type I alcoholism). This result was based on an analysis of data from the relatives of female and male alcoholics (i.e., the alcoholics were the primary subjects, or probands) in their study of families of alcoholics. Gilligan and colleagues concluded that greater genetic involvement was present within the families of male alcoholics than within the families of female alcoholics. More over, they concluded that two types of alcoholism existed in males, but only one type occurred in females. The researchers did not, however, test for more than one type of inheritance to explain the trans mission of alcoholism among the female proband families. Thus, assumptions about the existence of only a single form of alcoholism in women may have been premature (Aston and Hill 1990a).
The alcoholism field appears to have accepted the view of two types of male alcoholism while assuming, with a few notable exceptions (Glenn and Nixon 1991;Hill and Smith 1991;Lex et al. 1991), that only one type of alcoholismone without a genetic etiology-exists in females. In fact, as suggested above, the familial form of alcoholism that appears to exist in women resembles the familial form (i.e., type II) seen in men. Evidence of familial transmission is readily apparent for cases in which alcoholism severity is greater. For example, in families having members with early onsettype alcohol ism, in which multiple afflicted relatives are present (sometimes in multiple genera tions), the tendency for alcoholism to run in families is clear. Nevertheless, familial transmission still could be a result of common familial environmental factors rather than genetic ones. Although the data needed to draw firm conclusions about female alcoholism are missing, the litera ture reviewed above suggests that alco holism can be genetically mediated in women. Lateonset alcoholism in women may well be influenced more by environ mental factors (e.g., divorce or loss of maternal role in middle age [emptynest syndrome]) than by genetic factors. To lend support to the existing evidence for more than one (i.e., heterogeneous) form of female alcoholism, detailed studies of the genetic aspects of alcoholism in wom en and in their families have been con ducted and are discussed below.
It may be concluded that the etiology of female alcoholism has as much likeli hood of being mediated through genetic factors as does men's (Hill 1993). The evidence for genetic mediation includes two twin studies of female alcoholism in which heritability was found to be signifi cant (Pickens et al. 1991;Kendler et al. 1992) and an adoption study (Cadoret et al. 1985). Moreover, alcoholism appears to be heterogeneous in women, with one form (the early onset type) much more likely to be influenced by genetic factors than the other (lateonset) form (Glenn and Nixon 1991;Lex et al. 1991;Hill and Smith 1991).

GENETIC MEDIATION OF ALCOHOLISM IN WOMEN: POTENTIAL RISK MARKERS
The process of becoming alcoholic still may be different for women than for men (Hill 1993). This possibility suggests a need to search for markers of vulnerability for women as well as for men. Finding biological markers of alcoholism risk that are minimally affected by environmental factors (e.g., exposure to an alcoholic parent, sibling, or other family member) could prove useful in understanding the relative contribution of genetic factors to vulnerability for alcoholism. Additionally, these markers could be utilized in preven tion efforts by providing a screen for alcoholism susceptibility.
The search for useful markers of "risk" would be facilitated by the identifi cation of a physiological trait in alco holics that differs from nonalcoholics. Also, finding a marker that discriminates high from lowrisk persons who are not themselves alcoholic is an important step in this process. Ideally, one also would like to find a marker that is under genetic control. Locating neurobiological mark ers of vulnerability in women and girls is especially useful if susceptibility varies by gender.

History of EventRelated Potential Research
One biological tool that has proved useful for investigating markers of alcoholism is measurement of the eventrelated potential (ERP) of the brain. The ERP is measured with the electroencephalogram (EEG), which amplifies the naturally occurring brain electrical activity at the scalp. The ERP is graphically displayed on a scan as a wave with several peaks and valleys (see figure 1). ERP's occur in response to sen sory, motor, or cognitive events. One component, the P300, is one of the posi tive peaks on the ERP wave and occurs approximately 300 milliseconds (ms) after an informative event. In laboratory tests, the P300 is elicited by asking a subject to respond to an unusual stimulus (e.g., "oddball" paradigms: a high tone in a series of low tones or a red circle in a series of green circles) by performing a simple task (e.g., pressing a button or counting the high tones).
Researchers have examined the P300 both in alcoholics and in nonalcoholic persons at high risk for developing alco holism. These studies have observed whether the relationship between being an alcoholic or being a highrisk nonalcoholic person is associated with reduced height (i.e., amplitude) of the P300 wave or with the time it takes for the stimulus to be presented and the P300 peak to occur (i.e., the P300 latency). P300 latency changes generally accompany exposure to neuro toxic substances such as alcohol. Thus, latency changes can be associated with recent exposure to alcohol. ERP studies in male chronic alcoholics have shown evi dence for a reduction in P300 amplitude in some investigations (Porjesz and Begleiter 1981), but not in all studies (Pfefferbaum et al. 1979;Hermanutz et al. 1981;Lille et al. 1987;Hill et al. 1988Hill et al. , 1995b. Because alcoholics consume alcohol for extensive periods of time and at varying intervals before testing, uncovering P300 differ ences that may have existed before the onset of abusive drinking is not always possible. Numerous studies, however, have demonstrated deficits in the P300 component in nonalcoholic highrisk children and adolescents. Prior to a report from Hill and colleagues (1995a), re searchers had found the P300 deficit only in the offspring of male alcoholics (Begleiter et al. 1984;Whipple et al. 1988;Hill et al. 1990;Hill and Steinhauer 1993a;Steinhauer and Hill 1993).
The ERP, and the P300 component in particular, has value as a marker of alco holism for two reasons. First, ERP's are associated with particular sensory and cognitive aspects of information process ing. These processes may be affected in people at risk for alcoholism. Second, the ERP wave form has been found to be more similar between family members than between unrelated people. Thus, it appears to be under genetic control (Steinhauer et al. 1986;Polich and Burns 1987;Aston and Hill 1990b) and is unlike ly to be influenced by environmental factors. Someone whose P300 amplitude is reduced and who is from a family with a high density of alcoholism could have an inherited risk of developing the disease. Thus, reduced P300 in women at high risk for developing alcoholism could lend support to the idea that the disease can be genetically mediated in women.
Two studies have examined the P300 component in alcoholic women (Parson et al. 1990;Hill and Steinhauer 1993b). One of these (Hill and Steinhauer 1993b) looked at highrisk relatives of alcoholic women for possible P300 alterations, finding P300 amplitude deficits among the alcoholic women. Parsons and col leagues (1990) compared ERP character istics of female alcoholics with those of female nonalcoholic control subjects using auditory and visual paradigms but found no differences in P300 amplitude or latency.

THE BIOLOGICAL FACTORS FAMILY STUDY OF FEMALE ALCOHOLISM
Considering the evidence both questioning and/or supporting the existence of a severe form of genetically influenced alcoholism in women, and given the usefulness of the P300 as a potential marker for genetic vul nerability, Hill and colleagues designed a study to examine the nature of female fa milial alcoholism. They investigated the presence of a severe form of alcoholism and its relationship to any effects on P300 waves among women and children from families in which a high concentration of female alcoholics was present.

Criteria for Families
In the study, multiple extended families with multigenerational alcoholism were located over a 6year period as part of the Biological Risk Factors Family Study (figure 2). One goal of this research has been to identify neurobiological indicators of risk, such as the P300, in alcoholic women and their relatives who are at high risk of developing the disease, particularly minor children from these families.
In contrast to the methodology used by Parsons and colleagues (1990) (mentioned earlier; wherein the FHP designation could refer to just one alcoholic relative being present in a woman's family) Hill and col leagues' study ascertained FHP histories with the intention of finding families (i.e., pedigrees) with a high density of alcoholic members ( al. in press). The highrisk families in the study were found initially through a pair of female alcoholic siblings. This strategy results in the greatest chances of alco holism occurring across generations with in the same family. At least one member of each pair was in treatment for alco holism when identified; if an alcoholic sibling did not exist, the presence of other alcoholic female relatives sometimes enabled the family to be included. All probands and firstdegree relatives (i.e., parents, siblings, and children) included in the study were required to be largely free of psychiatric disorders (i.e., recurrent depression and schizophrenia were condi tions for exclusion). 4 This requirement ensured that the neurobiological markers found would be specific to alcoholism and not to general "psychiatric morbidity." In addition, possible sources of variation were evaluated in all study participants, including socioeconomic status, familial environment, and menstrual cycle phase, along with overall neuropsychological test performance, to ensure that any differ ences between the groups did not result from these variables. All firstdegree, adult relatives (both alcoholic and nonalcoholic) of the treated alcoholic women were studied. The chil dren studied were the offspring of the alcoholic subjects and their siblings. To arrive at a diagnosis with respect to alco holism and other psychopathology, two interviews were conducted, or two family 4 Psychiatric disorders were defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Third Edition. history reports were gathered for each relative. The age of onset of alcoholism for women in this study was quite early, with a median of 16 years (Hill 1993). 5 Because the study families were chosen for their high frequency of alcoholism (a minimum of two alcoholic members per family), the researchers hypothesized that the families' alcoholism would be genetically mediated (as was intended by research design). The study of highdensity families would maximize the likelihood of finding biologi cal markers, should they exist.
The control families (i.e., the lowrisk families) were selected for minimal psy chopathology (including alcoholism) among the sister pairs and their first degree relatives. These families were selected so that general psychiatric disor ders in the high and lowrisk groups were equivalent (for further review of the meth ods involved in this study, see Hill 1993;Hill and Steinhauer 1993a;Steinhauer and Hill 1993).

EVENTRELATED POTENTIALS
To verify their hypothesis that the alco holic women did have a genetically influ enced form of the disease, the researchers observed ERP's in the women and in their children. Adult women and minor children from the high and lowrisk pedigrees were evaluated using identical tests and recording conditions (one visual task and 5 In the general population, onehalf of all alcoholic women experience onset after the age of 45, whereas for men, onehalf are alcoholic by age 30 (Helzer et al. 1991). two listening tasks), enabling the assess ment of important developmental and gender differences in P300 waves.

ERP Differences in Alcoholic Women, Nonalcoholic Sisters, and Controls
One phase of the study investigated possi ble differences in P300 that might be associated with alcoholism risk (Hill and Steinhauer 1993b). The subjects studied included 25 alcoholic women, 31 of their highrisk nonalcoholic sisters, and 30 control women from lowrisk families.
Amplitude Is Reduced. The P300 ampli tude elicited from one auditory task was reduced significantly for the alcoholic women compared with the control wom en and their nonalcoholic sisters. For the other auditory and the visual task, alcoholic women also were found to have reduced P300 amplitude compared with their nonalcoholic sisters. P300 latency did not differ by group. This suggests that group differences in P300 did not result from differences in recent exposure to alcohol. The findings from this portion of the study suggest that reduction in P300 amplitude occurs only in alcoholic women.

Significance of Findings.
The difference between the P300 amplitude of alcoholic women and that of their nonalcoholic sisters is of considerable significance. Although the reduction could result from the longstanding use of alcohol leading to neuropathological changes, this possibili ty appears unlikely because the women showed equal ability on tests of neuro psychological functioning. Any genetic influence on women in these families may be inherited by one sister and not by the other. In addition, a recent analysis of a large data set from alcoholic men, their highrisk brothers, and nonalcoholic controls showed no P300 amplitude re duction in adult males (Hill et al. 1995b), a result also found by others (Pfefferbaum et al. 1979;Hermanutz et al. 1981;Lille et al. 1987). These results have led to speculation that P300 differences in high risk populations may represent delays in development of cognitive functioning that typically are seen only in childhood. In contrast to findings in men, women who became alcoholic in adolescence persist in having reduced P300 amplitude in adult hood. Further research is needed to exam ine the possible gender differences (e.g., differences in the hormonal system) that might account for this phenomenon. At any rate, women alcoholics display clear ly different neurophysiological character istics from their nonalcoholic sisters, a condition that may have its antecedents in childhood. Demonstration of differences in childhood, prior to the initiation of drinking, would provide further evidence that the marker has etiological signifi cance and is not merely a consequence of drinking.

P300 in HighRisk Children From Female Alcoholism Families
Because alcoholic women exhibit P300 amplitude reduction, their children also might have reduced P300, possibly indicating a genetic risk for developing alcoholism.
Subjects. Seventysix children ages 8 to 18 were studied. Two groups of children (whose mean age was 11.3) were drawn from the highrisk families and the control families. Both groups contained 38 chil dren: 17 males and 21 females. All chil dren were free of alcohol and other drug (AOD) use at the time of testing, and only one child was a regular AOD user. 6 Because the mothers of both groups of children could have consumed alcohol during pregnancy, the study design includ ed interviewing all mothers (even those who were social drinkers) about current and lifetime AOD use to determine AOD use during pregnancy. Mothers of 12 high risk children reported drinking during pregnancy (2 of the mothers also had used marijuana), and mothers of 26 children denied AOD use during pregnancy.
Results for an Auditory ERP Task. The P300 peak was studied in 35 highrisk children and 35 control children (matched in age). A significant effect was found in one task, in which the amplitude for the highrisk group was lower than that for the lowrisk group (Hill et al. 1995a). To control for prenatal alcohol exposure, data were reanalyzed to exclude the highrisk children whose mothers drank during pregnancy and their corresponding con trols. Group differences remained even in this smaller sample of 24 children of mothers who reported abstinence when compared with control subjects. Thus, the P300 amplitude reduction in highrisk children appears to result from a familial vulnerability and not from prenatal alco hol exposure.

Reduced P300 Amplitude in Girls From
Female Alcoholism Families. Because the study also was intended to discern whether female children would exhibit ERP char acteristics similar to those found previously among highrisk male children, it focused on reanalyzing data with respect to P300 differences in daughters of alcoholic mothers (figure 3). Because a reduction in P300 amplitude might result from the joint in fluence of having a biological mother and father who both were alcoholic, for this analysis, girls who had an alcoholic father were excluded. Female children with alcoholic mothers did display reduced P300 amplitude (Hill et al. 1995a).
The P300 results from the girls with alcoholic mothers suggest that the same neurobiological indicators of risk found in children from highdensityformale alcoholism families (Hill and Steinhauer 1993a;Steinhauer and Hill 1993) are risk indicators in the highdensityforfemale alcoholism families. Interestingly, com pared with lowrisk boys, a greater proportion of highrisk boys exhibit P300 amplitude below the median of the control subjects (approximately one in three). A similar comparison for girls showed that approximately one in six highrisk girls exhibited P300 below the median of the controls. Thus, because alcoholism among females is less prevalent in the general population than it is among males, one would expect the ratio of girls to boys showing P300 reduction to be comparable to the ratio of female to male alcoholics in the general population. Although this study of offspring of alcoholic women has not yet followed the children prospective ly, P300 appears to predict clinical out come for alcohol dependence. This  in highrisk children compared with con trol subjects (Hill et al. 1990;Hill and Steinhauer 1993a;Steinhauer and Hill 1993). Recent research has shown that children of female alcoholics display similar P300 amplitude reduction (Hill et al. 1995a). This finding suggests that P300 is a neurobiological marker for genetic alcoholism risk in children from both male and female alcoholism families.

RESEARCH UPDATE
Comparison of the clinical and psycho pathological characteristics of children from highrisk pedigrees, in which ap proximately 50 percent of both male and female relatives are alcoholic, reveals that these children are at greatly increased risk for childhood psychiatric disorders rela tive to controls. This conclusion stands in contrast with the more modest differences in psychopathology reported for children from highrisk families located through male alcoholics (Hill and Hruska 1992).
Thus, it appears that the consequences of being a child of an alcoholic woman are represented by significant neurobiological markers of risk (e.g., reduction in P300 amplitude) and psychopathological condi tions that may promote alcoholism. ■

ACKNOWLEDGMENTS
The author wishes to thank J. Locke, S. Gronlund, and E. Blauser for their excel lent technical assistance and T. Smith, D. Muka, and L. Lowers for recruiting subjects and assisting in clinical evalua tions. She also wishes to thank H. Yuan, Ph.D., C. Aston, Ph.D., and S. Steinhauer, Ph.D., for their continued support and collaboration. Also, the research group is indebted to the families who participated and to the treatment centers who allowed them to recruit families from their patient populations.